An Oklahoma born in 2010 has the fifth lowest life-expectancy in the US and American Indians have the shortest, 7.3 years less than the US average. Cancer, diabetes, cardiovascular disease, arthritis, and autoimmunity are leading causes of disability and early mortality, serving as sources of major health disparities in Oklahoma and other IDeA-states. Along with these diseases, tobacco use, opioid abuse, and child health are also prominent health concerns. The primary mission of the Oklahoma Shared Clinical and Translational Resources (OSCTR) is to improve health by catalyzing clinical and translational research (CTR) in these top health priorities. To fulfill its mission, the OSCTR integrates health professionals, investigators, and scientific resources at 29 public, private, and tribal partners/affiliate partners statewide. Oklahoma is an ideal setting for these efforts due to these high rates of chronic diseases, and large rural and tribal populations where improved health outcomes may serve as models across IDeA states. CTR on tribal health priorities and health equity is fostered by strong relationships between OSCTR research institutions and tribal nations/health systems. OSCTR houses the only CAP-certified biorepository affiliated with an IDeA-CTR, and cutting-edge resources for data research and medical data warehouses. Oklahoma also has a growing cadre of junior investigators who are launching independent CTR careers (most with OSCTR assistance), with institutional leaders who are committed to CTR and improving Oklahomans health. Concurrent with these strengths, the OSCTR is leveraging new partnerships to move toward prevention. Although many early successes are evident, CTR sustainability in Oklahoma and its impact on public health are limited by ongoing needs for infrastructure support and by a need for further development of the nascent clinical research infrastructure. Therefore, to expand research into diseases with high prevalence in rural and tribal populations, the OSCTR is helping tribal health systems build CTR infrastructure and fostering interactions through the Tribal Engagement Unit. To launch independent CTR careers of junior investigators from multiple disciplines, the OSCTR provides training, mentoring, pilot grants, and infrastructure. This includes patient registries, repositories, and data warehouses; recruiting and regulatory support; biostatistical and epidemiologic expertise; and comprehensive online resources linking investigators to relevant Core facilities at each OSCTR partner institution and Oklahoma IDeA program. To engage health professionals, communities, and patients in high-priority CTR, the OSCTR will develop an expanded online portal to educate patients and providers on CTR, and leverages a large network of community-oriented health improvement organizations. Finally, to develop and share effective infrastructure, the OSCTR collaborates with biomedical IDeA programs in Oklahoma and other states. Together, these activities will help develop a critical mass of investigators to sustain Oklahoma?s CTR infrastructure with a combination of federal funding, industry-sponsored clinical trials, and local support.